Inflammation Research

, Volume 67, Issue 6, pp 539–551 | Cite as

A large lung gene expression study identifying IL1B as a novel player in airway inflammation in COPD airway epithelial cells

  • Gao Yi
  • Min Liang
  • Ming Li
  • Xiangming Fang
  • Jifang Liu
  • Yuxiong Lai
  • Jitao Chen
  • Wenxia Yao
  • Xiao Feng
  • La Hu
  • Chunyi Lin
  • Xinke ZhouEmail author
  • Zhaoyu LiuEmail author
Original Research Paper



Chronic obstructive pulmonary disease (COPD) is a chronic and progressive lung disease characterized by a mixture of small airway disease and lung tissue parenchymal destruction. Abnormal inflammatory responses to cigarette smoking and other noxious particles are generally thought to be responsible for causing of COPD. Since airway inflammation is a key factor in COPD progress, it is crucial to unravel its underlying molecular mechanisms. Unbiased analysis of genome-wide gene expression profiles in lung small airway epithelial cells provides a powerful tool to investigate this.


Gene expression data of GSE611906, GSE20257, GSE8545 were downloaded from GEO database. All 288 lung small airway samples in these cohorts, including donors with (n = 61) and without (n = 227) COPD, were chosen for differential gene expression analysis. The gene ontology (GO) function, Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses, gene co-expression network analysis (WGCNA) and protein–protein interaction (PPI) network analysis were performed. Subsequently, the analyses of IL1B expression level, the Pearson correlation between IL1B and several COPD biomarkers were performed using other cohorts to validate our main findings.


With a change ≥ twofold and P value < 0.05 cutoff, we found 38 genes were up-regulated and 114 genes were down-regulated in patients with COPD compared with health controls, while using cutoff fold change 1.5 and P value < 0.05, there were 318 genes up-regulated and 333 genes down-regulated. Among the most up-regulated genes were IL1B, CCL2, CCL23, and CXCL14, all implicated in inflammation triggering. GO, KEGG and WGCNA analysis all disclosed IL1B was highly correlated to COPD disease trait. The expression profile of IL1B was further validated using independent cohorts from COPD airway epithelium, lung tissue, sputum, and blood. We demonstrated higher IL1B gene expression in COPD small airway epithelial cells, but not in COPD lung tissue, sputum, and blood. Strong co-expression of IL1B with COPD biomarkers, such as DUOX2, MMP12, CCL2, and CXCL14, were validated in silico analysis. Finally, PPI network analysis using enriched data showed IL1B, CCL2, CCL7 and BMP7 were in the same hub node with high degrees.


We identified IL1B was significantly up-regulated in COPD small airway epithelial cells and propose IL1B as a novel player in airway inflammation in COPD.


IL1B COPD Airway epithelial cells Inflammation 



Interleukin 1 beta


Interleukin-1 receptor type 2


Chronic obstructive pulmonary disease


Chemokine (C-C motif) ligand 2


Chemokine (C-C motif) ligand 7


Chemokine (C-C motif) ligand 23


Hypoxia inducible factor-1 alpha


Differentially expressed genes


Glyceraldehyde-3-phosphate dehydrogenase


Aldehyde dehydrogenase 3 family, member A1


Dual oxidase 2


Matrix metalloproteinase 12


Aldo–keto reductase family 1, member B10


Cytochrome P450 family 1 subfamily B polypeptide 1




Protein–protein interaction


Gene significance


Module membership


Gene set enrichment analysis




Cytochrome P450


Gene ontology


Kyoto Encyclopedia of Genes and Genomes


Weighted Gene Co-expression Network Analysis



We thank all members from department of central laboratory, the Fifth Affiliated Hospital of Guangzhou Medical University for their invaluable help.

Author contributions

ZYL, XKZ and JFL designed the study; ML (Min Liang), ML (Ming Li) and XMF performed data collection; GY and YXL analyzed the data; ZYL and GY wrote the manuscript. All authors read and approved the final manuscript.


This work was supported by the National Natural Science Foundation of China (Grant Number. 81400013), Science and Technology Planning Project of Guangdong Province, China (Grant Number. 2014A20212329) and Department of education of GuangDong Province, China (Grant Number. 2016KTSCX110).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical approval and consent to participate

In the current study, all analyses were based on publicly available data, and this article does not contain any studies with human participants and animals performed by any of the authors.

Consent for publication

Not applicable.

Supplementary material

11_2018_1145_MOESM1_ESM.xlsx (23 kb)
Supplementary material 1 (XLSX 22 KB)


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Respiratory Medicine, State Key Laboratory of Respiratory DiseaseThe Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina
  2. 2.Department of Center LaboratoryThe Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina

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